Ureaplasma urealyticum, erythromycin and respiratory morbidity in high-risk preterm neonates.

We investigated colonization with Ureaplasma urealyticum (Uu) in infants <30 weeks gestation and assessed the relationship to other risk factors influencing respiratory morbidity, plus the effect of treatment with erythromycin. Ventilated preterm infants [n = 155; median GA 26 (23-29) weeks] were cultured for Uu in endotracheal aspirate and nasopharynx. Colonized infants were randomly assigned to treatment with erythromycin 40 mg/kg/d, intravenously or orally. The rate of colonization was 29/155 (19%) and the Uu-colonized infants had lower mean gestational ages than the culture-negative infants (25 vs 26 weeks). For the colonized infants PROM (48% vs 12%), chorioamnionitis in the mother (46% vs 17%) and vaginal delivery (71% vs 29%) were more common. More colonized infants needed supplemental oxygen at 36 weeks' postconceptual age (p < 0.05). Erythromycin treatment was effective in reducing colonization with negative control cultures in 12/14 (86%) of treated infants. No significant differences were found between the colonized treated infants (n = 14) and those not treated (n = 14) in time with supplemental oxygen. Oxygen requirement at 36 weeks was related to lower gestational age, late appearance of PDA, late onset sepsis and signs of chorioamnionitis in the mother. We conclude that the Uu colonization is related to increasing immaturity, the presence of prolonged rupture of membranes, signs of chorioamnionitis and vaginal delivery. Treatment with erythromycin reduced colonization but did not significantly alter length of time with supplemental oxygen.

Neonatal care of very-low-birthweight infants in special-care units and neonatal intensive-care units in Stockholm. Early nasal continuous positive airway pressure versus mechanical ventilation: gains and losses.

Very-low-birthweight (VLBW) infants are usually intubated at birth and mechanically ventilated at neonatal intensive-care units (NICUs). The objectives of this study were to evaluate the use of early nasal continuous positive airway pressure (NCPAP) in a regional cohort and to determine to what extent VLBW infants need transfer to a regional NICU from special-care units (SCUs) that primarily use early NCPAP for respiratory care. We compared the outcome for infants at SCUs and NICUs in Stockholm County, Sweden, from 1988 to 1993. All infants with birthweights of less than 1501 g were included in this study (n = 687). Fifty-nine per cent of the infants (400/687) were supported using only supplemental oxygen or NCPAP. Of these, 170 (25%) received only supplemental oxygen and 230 (34%) were supported only by NCPAP. A total of 350 (51%) infants received early NCPAP. Of these infants, 120 (34%) later required mechanical ventilation. Only 167 (24%) infants received mechanical ventilation from the beginning Failure of NCPAP was significantly associated with the presence of respiratory distress syndrome. A total of 161/412 (39%) infants were transferred from SCUs to NICUs. Of infants < or = 26 weeks' gestation and infants > 26 weeks, 71% and 34% were transferred, respectively. Total mortality was 16%. The mortality for transfers was 20% compared to an overall mortality in SCU and NICU infants of 9% and 15%, respectively. The overall incidence of intraventricular haemorrhage (IVH), grade III-IV was 8%, periventricular leucomalacia (PVL) grade I-IV was 7%, retinopathy of prematurity (ROP) requiring cryotherapy was 4.3% and chronic lung disease (CLD) was 14%. There were significant differences in the incidence IVH, PVL, CLD and ROP between SCU and NICU infants in matched gestational age groups. In conclusion, infants with a gestational age of 27 weeks or more may often be adequately cared for at SCUs without mechanical ventilation by using early NCPAP. However, infants with a gestational age of 26 weeks or less should be transferred to tertiary-care centres preferably before birth, because they will often require mechanical ventilation.

Neonatal Ureaplasma urealyticum colonization and chronic lung disease.

We studied Ureaplasma urealyticum colonization in 93 intubated infants (gestational ages 23-40 weeks) in our neonatal intensive care unit by obtaining cultures from endotracheal aspirate and nasopharynx during their first week of life. Eighteen infants had positive cultures, giving a colonization rate of 19%. No infant more than 30 weeks' gestation had a positive culture. The infants with positive cultures had a significantly lower gestational age and birth weight (p < 0.009 and p < 0.005), with a colonization rate of 33% in infants less than 1000 g. Among the infants with positive cultures, 10 of 17 developed chronic lung disease in contrast with 21 of 72 infants with negative cultures. The development of chronic lung disease and duration of oxygen requirement was strongly associated with immaturity but only weakly with Ureaplasma urealyticum.

Comparison of outcome of labetalol or hydralazine therapy during hypertension in pregnancy in very low birth weight infants.

Ninety-seven women with moderate to severe preeclampsia (PE) were allocated at random to labetalol or hydralazine treatment. Of these, 22 women with severe PE gave birth to neonates with VLBW (very low birth weight < or = 1500 g). Seven were allocated to labetalol treatment (Group A), eight to hydralazine treatment (Group B) and seven women received both drugs due to poor blood pressure control with a single drug therapy (Group C). No difference in cesarean section rate or in the indication for operative delivery could be seen. Gestational age was 29.9 weeks (25.4-32.5) in Group A, 28.6 weeks (26.6-33.4) in Group B and 27.3 weeks (26.7-31.1) in Group C (median and range). Birth weight did not differ between groups and 13 of the 22 infants weighed below 1000 g. There was a tendency to lower Apgar scores at five minutes in the hydralazine group. Time spent in the neonatal intensive care unit did not differ between groups. Five of the 11 neonates with gestational age (GA) < or = 28 weeks and three of the seven neonates in GA 29-30 weeks died. Neither the number of infants requiring intermittent positive pressure ventilation or duration of O2- treatment, nor number of infants with respiratory distress syndrome differed between groups. We did not find any difference in the outcome of the VLBW infants when the hypertensive mother had been treated with either hydralazine or labetalol.

Neonatal adaptation in hypertensive pregnancy--a study of labetalol vs hydralazine treatment.

Twenty mothers with moderate to severe preeclampsia were allocated to labetalol (Trandate) or hydralazine (Apresolin) antihypertensive treatment. Arterial blood gas analysis was performed at delivery from the clamped cord. Neonatal blood pressure, heart rate and axillary temperature were registered 0.5, 2, 6, 12, 24, 36, 48 hours and 3, 4 and 7 days after birth. Respiratory rate was registered at the same intervals until 36 hours after birth. Blood glucose levels were measured 2, 6, 12 and 24 hours after birth. Peripheral blood flow in the calf was measured at 24 hours of age. Gestational age did not differ between the two groups; 36 (27-40) in the labetalol, and 35 (29-37) weeks in the hydralazine group (median and range). Median cord pH was lower, and the number of infants with a cord pH < 7.20 was higher in the hydralazine group. Blood glucose levels were lower in the labetalol group at 6 hours of age (p < 0.05). No other differences were found between the two groups. The conclusion is that no clinical signs of adrenergic blockade have been found at 24 hours of age, and no negative effect of labetalol on the neonatal adaptation compared to hydralazine antihypertensive treatment was found.

Colonization with coagulase-negative staphylococci in two neonatal units.

Episodes of septicaemia due to coagulase-negative staphylococci (CNS) were more frequent in a level III than in a level II neonatal unit in Stockholm, Sweden. Colonization with CNS during the first 2 weeks of life was investigated in 10 infants from each unit. As the use of antibiotics differed between the two units, the aim was to correlate colonization and antimicrobial resistance patterns to antibiotic usage. Antimicrobial susceptibility of CNS to isoxazolylpenicillins, co-trimoxazole, erythromycin, clindamycin, chloramphenicol and gentamicin was determined. Selected isolates were typed with restriction endonuclease analysis of plasmid DNA and of genomic DNA. Infants were frequently colonized with multiple strains and species of CNS, and transmission of strains from patient to patient occurred within the unit. Qualitative and quantitative differences in antibiotic use were not correlated with colonization. The prevalence of resistant isolates, mostly of Staphylococcus haemolyticus, was higher in the level II unit with lower use of antibiotics. Staphylococcus epidermidis, which is generally more virulent, prevailed in the level III unit, where there were more severely ill children and invasive procedures were more frequently performed.

Psychological development in children born with very low birth weight after severe intrauterine growth retardation: a 10-year follow-up study.

Children born small for gestational age (SGA) and children having very low birth weight, less than 1500 g, are claimed to be at risk of developmental problems, even when obvious pathology and disability are absent. In this study, sensorimotor and cognitive development of 14 medically healthy, very-low-birth-weight and small-for-gestational-age children were investigated. The children were born at the Karolinska Hospital between 1979 and 1981. At the time of the assessment, the children were aged 8.7-11.2 years. The assessment instruments included the Wechsler Intelligence Scale for Children, a modified version of the Bruininks-Oseretsky Test of Motor Proficiency, as well as selected subtests from the Halstead-Reitan Neuropsychological Battery and from the Southern California Tests of Sensory Integration. Information was also obtained from obstetric, neonatal and pediatric records, which included early developmental assessments. As a control group, 14 children were recruited and matched for age, sex and socio-economic background. The very-low-birth-weight-small-for-gestational-age group scored significantly lower on measures of visuospatial ability, non-verbal reasoning, strategy formation and gross-motor coordination. The group differences were largely attributable to the subnormal performance of eight of the very-low-birth-weight-small-for-gestational-age children. These children, who also tended to be born earliest (less than 33 weeks), had a high incidence of behavioral and educational problems. These findings are consistent with the view that the very preterm infant develops a different neurobehavioral organization than a full-term infant. Developmental deficits may become increasingly evident in the early school years.

Nosocomial Staphylococcus epidermidis septicaemia among very low birth weight neonates in an intensive care unit.

A cluster of cases of septicaemia caused by coagulase-negative staphylococci was observed among the infants at the Neonatal Intensive Care Unit (NICU) of the Karolinska Hospital in May 1987. The presence of a unique antibiogram among the blood culture isolates prompted an investigation to determine whether an epidemic strain existed or not, using antibiogram, biotyping and plasmid profiles as epidemiological markers. All 14 isolates with a unique antibiogram were investigated, and 22 isolates without the unique antibiogram served as controls. Of the 14 isolates, 11 were Staphylococcus epidermidis and had similar plasmid patterns. Of the 22 control isolates, 15 were S. epidermidis, and none had the special plasmid pattern nor any other recurring plasmid patterns. The use of plasmid profile analysis together with antibiograms thus identified a possible epidemic strain of S. epidermidis which may have been responsible for the upsurge of septicaemia cases at the NICU. The presence of an epidemic strain implies that hospital cross infection control could be important in preventing neonatal septicaemia caused by S. epidermidis.

The role of a commercial latex agglutination test in the diagnosis of group B streptococcal infection in neonates.

An open prospective multicenter study was conducted in order to evaluate the Wellcogen Strep B latex agglutination test in the diagnosis of group B streptococcal (GBS) infections in neonates. Twenty-three (5.9%) of 391 urine specimens and 5 (1.2%) of 404 sera assayed were positive. The results of the urine tests corresponded to a sensitivity of 0.78 for bacteremic, 0.50 for non-bacteremic and 0.53 for all GBS associated (bacteremic, non-bacteremic and suspected) infections. After 20-25-fold concentration of urine specimens the sensitivity increased to 1.0 for bacteremic, 0.67 for non-bacteremic and 0.78 for all GBS associated infections. The specificity of the test was high (0.93 for concentrated urines), and the predictive value of a positive test (Pvpos) was 0.68. A positive latex test was highly predictive of positive surface cultures for GBS (Pv pos = 0.83 after concentration).

WISC-test scores at the age of 10 for children born to women with risk pregnancies.

The subjects (N = 50) were born to mothers who had earlier participated in an extensive clinical investigation during their pregnancies. Maternal serum hormone levels were investigated from pregnancy week 20 and on to partus. Fourteen children were born small-for-gestational age (SGA) and eight pre-term appropriate-for-gestational age (AGA). Each SGA child had two control children, born to mothers with normal or high serum levels of alpha-fetoprotein (AFP) in pregnancy week 16-17. Elevated serum levels of AFP was considered to be a sign of fetal stress. All 50 children were administered the WISC-test at 10 years of age. The SGA children had lower scores than control children in Performance and Full scale scores. The pre-term SGA children had lower scores than the controls in Verbal, Performance and Full scales. That was not the case for on-time SGA and pre-term AGA children. Girls born to smoking mothers performed less well than girls of non-smoking mothers on the Verbal scale. Positive correlations of maternal serum hormone levels (oestriol, hCG, and hPL) and WISC-test scores were present for girls. For boys a single maternal hormone in pregnancy (prolactin) was correlated with WISC-test scores at 10 years of age.

Septicaemia with coagulase negative staphylococci in a neonatal intensive care unit. Risk factors for infection, and antimicrobial susceptibility of the bacterial strains.

Septicaemia caused by coagulase negative staphylococci is a problem in the neonatal intensive care units (NICU). The very low birthweight (VLBW) infants are at a special high risk because of their immature host defense. In this study the potential risk factors were compared between the VLBW septicaemia patients and the VLBW infants who had not contracted septicaemia in the NICU. The factor most clearly related with septicaemia was the use of umbilical artery catheters. The strategy against neonatal septicaemia includes restriction of the use of intravascular catheters. Also enhancement of the host defense by immunoglobulin therapy is considered. The coagulase negative staphylococci were multiresistant to antibiotics. The combination of netilmicin and benzylpenicillin covered the bacteria found in septicaemia cases in the NICU, and is now the standard treatment in suspected cases. Coagulase negative staphylococci are treated with vancomycin or netilmicin.

Neonatal septicemia due to group B streptococci--perinatal risk factors and outcome of subsequent pregnancies.

All cases of early onset group B streptococcal (GBS) septicemia in infants born at Karolinska Hospital 1975-1986 were reviewed. GBS-septicemia was diagnosed in 40 infants within the first five days of life. The incidence was 1.24 per 1000 births. Fifty-five percent of the infants were preterm and 48% were born more than or equal to 12 hours after rupture of membranes. Prematurity and/or prolonged rupture of membranes were present in 83% of all neonates with fatal outcome. Case fatality was 22%. Deliveries by both cesarean section (31%) and vacuum extraction (26%) were increased in the mothers when compared to an overall incidence of 14 and 12% (p less than 0.01). Twenty-four (89%) of 27 mothers had low type specific IgG antibodies against the infecting GBS-serotype. Late onset GBS-septicemia was diagnosed in only two infants during the period. Seventeen mothers went through 24 subsequent pregnancies. In 11 of those the mothers were colonized with GBS and 10 received penicillin prophylaxis during pregnancy and/or delivery. None of the infants born after prophylaxis were colonized with GBS. Two were born prematurely and all had an uneventful course; whereas one infant delivered at 26 weeks gestation of a colonized untreated mother died of GBS-septicemia. Screening of parturients at risk and selective antibiotic prophylaxis may help to prevent early onset GBS-septicemia.

Neonatal septicemia in Stockholm.

In a prospective study to determine the incidence and etiology of neonatal septicemia at Karolinska Hospital, Stockholm, all cases of neonatal septicemia in infants born at the hospital from 1981 to 1985 were reviewed. There were 4.0 cases of neonatal septicemia per 1,000 live births during the study period. During the five year period the incidence of septicemia tended to increase, mainly due to the increasing incidence of septicemia in infants with a birth weight below 1,500 grams. The single most common causative organism was group B streptococci with an incidence of 1.4 per 1,000 live births, Staphylococcus aureus accounting for 1.1 cases, Staphylococcus epidermidis for 0.7 cases, and gram-negative rods for only 0.4 cases per 1,000 live births. In a retrospective study of the incidence of neonatal septicemia in a non-selected patient population, all cases in the Stockholm area in 1983 were reviewed. In that year there were 17,586 live births in the area and the incidence of neonatal septicemia was 2.6 per 1,000 live births. Group B streptococci, Staphylococcus aureus, Staphylococcus epidermidis and gram-negative rods were equally common as causative agents.

Immune response to pneumococcal vaccine in mothers to infants with group B streptococcal septicemia: evidence for a divergent IgG/IgM ratio.

Eight women who had given birth to infants contracting neonatal septicemia with group B streptococci (GBS) were immunized with a 14-valent pneumococcal vaccine (Pneumovax). Type-specific IgM and IgG antibodies against 6 pneumococcal types were determined before and after vaccination. Ten healthy age-matched women were also vaccinated and served as controls. The study group showed significantly higher preimmune IgM levels against 3 of the 6 pneumococcal antigens, and lower IgG levels against 1 antigen. However, 6 weeks as well as 11/2 years after the immunization, no significant differences in IgG or IgM antibody levels could be demonstrated between the 2 groups. Before vaccination, significantly more study group women showed an arbitrary IgG/IgM ratio below 10 against pneumococcal types 1, 6A, 7F, 14 and 23F. 11/2 years after vaccination, the ratio was significantly lower for antibodies against 2 other types, 6A and 7F. We suggest, as a working hypothesis, that mothers of GBS-infected infants differ in their capacity to switch from IgM to IgG production.

Catecholamine surge and metabolic adaptation in the newborn after vaginal delivery and caesarean section.

The immediate postnatal metabolic adaptation and sympatho-adrenal activation were studied in infants delivered vaginally or by elective caesarean section. Vaginally delivered infants showed high catecholamine levels at birth compared to infants born by caesarean section under epidural or general anaesthesia. Umbilical arterial glucose levels were significantly higher in the vaginal group than in both caesarean section groups. At 30 min, all groups showed a marked decrease with several infants showing asymptomatic hypoglycaemia in the caesarean section group. C-peptide levels showed no difference at birth but later became significantly higher in the vaginal group. Although the levels of free fatty acids and glycerol were low at birth, they were significantly higher in the vaginal group. In all groups they increased substantially with time. Considering the marked differences in catecholamine levels, the differences in metabolic adaptation were unexpectedly small. This implies an attenuated metabolic response to sympatho-adrenal stimulation in the newborn.

Transient increase of early-onset group B streptococcal septicemia.

Since 1976, all cases of neonatal group B streptococcal (GBS) septicemia/meningitis have been registered at two Swedish University Hospitals. A significant increase in the number of infants contracting early-onset GBS-septicemia was noticed at one clinic in 1981, from 1-3 cases per yr to 8 cases. Six months prior to this increase the number of deliveries increased from about 1500 per yr to nearly 3000 per yr. It is suggested that external factors, e.g., subtle changes in the nursing combined with an extended disadvantage at the ward might influence the development of early-onset GBS septicemia.

Sympathoadrenal activity and peripheral blood flow after birth: comparison in infants delivered vaginally and by cesarean section.

The possible influence of sympathoadrenal activity on peripheral blood flow was studied. Limb blood flow was measured with venous occlusion plethysmography at 30 minutes, 2 hours, and 24 hours after birth in 24 healthy, full-term infants, of whom 14 were delivered by elective cesarean section. Mean arterial pressure was simultaneously measured noninvasively, and peripheral vascular resistance calculated. Umbilical artery blood at birth and peripheral venous blood at 2 and 24 hours were analyzed for concentrations of catecholamines and hematocrit. The limb blood flow was significantly lower at 30 minutes in the vaginally delivered infants compared with those delivered by cesarean section. There was a gradual increase in limb blood flow over the 24 hours in those delivered vaginally, whereas in the section group only small changes were observed. The peripheral vascular resistance was higher both at 30 minutes and at 2 hours in those delivered vaginally, which corresponded to the higher catecholamine concentrations at birth and at 2 hours in this group. Two hours after birth there was a significant correlation between noradrenaline levels and peripheral vascular resistance. The results indicate that the sympathoadrenal system influences peripheral circulation at birth and is important in the circulatory adaptation of the newborn infant.

Neonatal left ventricular performance after vaginal delivery and cesarean section under general or epidural anesthesia.

Left ventricular systolic time intervals, plasma norepinephrine concentration, hematocrit, and blood pressure were recorded in infants delivered vaginally and by cesarean section from mothers under epidural or general anesthesia. Each group comprised 12 infants. Left ventricular ejection time and the preejection period were longer in infants delivered vaginally, although the concentrations of norepinephrine found were greater than those found in the cesarean section groups. Hematocrit and blood pressure were unrelated to the mode of delivery or the anesthetic technique. The isovolumic contraction time, however, was significantly shorter after epidural anesthesia 15.6 +/- 7.6 msec (mean +/- 1 SD) than after general anesthesia 20.5 +/- 8.0 msec at 30 minutes (p less than 0.05), 14.8 +/- 6.2 msec, and 20.9 +/- 5.7 msec at 2 hours respectively (p less than 0.001). These differences in left ventricular dynamics are probably related to the effects of anesthetics that have traversed the placenta rather than to mode of delivery.